The purpose of this proposal is to seek funds for the purchase of a triple quadrupole mass spectrometry system. This instrument will be a key component in the development of the new Laboratory of Mass Spectrometry within the Lerner Research Institute of the Cleveland Clinic Foundation (CCF). The requested mass spectrometer will be used to facilitate and advance research programs at institutions within the area (CCF, Case Western Reserve University (CWRU) and Cleveland State University (CSU)). Major Users all have NIH-funded research grants, which have component projects that can best be or only be conducted using mass spectrometry. Because of the significant limitation in access to instrumentation in the region, many Investigators have had to obtain access to this technology at remote institutions. As detailed in the application, the projects of Major Users are broad and include: 1) structural characterization of compounds; 2) quantification of structurally defined components in complex biological matrices; 3) characterization of covalent modifications of proteins, lipids and DNA by enzymatic, chemical and free radical-mediated mechanisms; 4) characterization of protein structure including investigations of receptor binding sites; and 5) investigations of macromolecular interactions. The requested mass spectrometer provides the versatility, sensitivity and specificity to meet these diverse demands. In addition, the requested instrument will be used to meet the needs of the occasional user. This analytical activity will be conducted within our existing Molecular Biotechnology Core, which provides support to investigators by performing protein sequencing, peptide synthesis, and related services. Mass spectrometry has been used as an analytical tool by an increasing number of investigators in the region. Thus, CCF, CWRU and CSU investigators have clearly recognized the value of mass spectrometry in their research programs. However, the limited access to shared instrumentation in the region has significantly hindered the pace of progress. The acquisition of the requested mass spectrometer is essential to take full advantage of the unique capabilities and usefulness of this instrumentation. CCF has committed substantial resources to the development of mass spectrometry in the region, including custom renovation of laboratory space for the Learner Research Institute Laboratory of Mass Spectrometry, personnel to oversee its operation, and a fiscal plan to insure its operation and maintenance for the long- term. In sum, acquisition of the requested mass spectrometry system will have a significant impact on the progress and future development of biomedical research programs at multiple institutions in the region including CCF, CWRU, and CSU.